This application seeks to continue an investigation of the mechanisms by which maternal nutrition affects fetal nutrient availability and fetal growth processes. We have documented a decrease in fetal cartilage 35S-sulfate uptake with both progressing gestation and in maternal fasting, unassociated with altered fetal serum growth-stimulating activity. We propose to investigate as possible explanations for this decreased skeletal growth activity changes in fetal cartilage somatomedin receptors, xylosyltransferase activity, acceptor protein, and/or circulating glucocorticoids or substrates. Using chronically instrumented sheep studied over a range of both gestation and maternal nutritional status, during the initial 2-year grant period we have described the apparent maximum capacity of the facilitated carrier mechanism of the placenta for glucose. We have shown that maternal insulin increases umbilical uptake of glucose, without altering lactate or amino acid uptakes. Thus, insulin appears to increase the permeability of the placenta to glucose and/or to stimulate the stereospecific hexose membrane transport system. We propose in vitro studies to prove insulin alters membrane transport in placenta. In addition, we propose to further investigate these observations with a series of in vivo and in vitro studies designed to answer the questions: (1) what is the function of membrane-associated insulin receptors in placenta (and other fetal organs) in regulating umbilical glucose uptake?, (2) is glutamine, not glucose, the source of placental lactate production?, (3) what is the fate of 50 percent of the glucose uptake by the placenta which does not enter the umbilical circulation?, and (4) what role does ovine placental lactogen present in both fetal and maternal circulations play in regulating fetal nutrient uptake, and is this effect species-specific? Other in vivo experiments have defined the ontogenic appearance of gastrin in fetal serum and tissues and have suggested that the fetal ontogeny may be influenced by maternal inhibitors which traverse the placenta. We will pursue this observation by studying the effect of maternal nutritional status on fetal gastrin and gut growth. Finally, we will begin studies of trace metal umbilical uptake in vivo and placental uptake kinetics in vitro to determine the mode of transplacental transfer, gestational changes, and the effect of maternal nutrition on these phenomena. We w (Text Truncated - Exceeds Capacity)